As is well known in the art, various prostheses are often employed to reconstruct or replace damaged or diseased cardiovascular vessels.
Currently, the prostheses often employed to reconstruct or replace damaged or diseased cardiovascular vessels are autologous arteries and veins, e.g., internal mammary artery or saphenous vein; particularly, in situations where small diameter (i.e. 3-4 mm) vessels are required, such as below the knee and coronary artery bypass grafting.
Autologous arteries and veins are, however, often unavailable, due to prior harvest, or unsuitable, due to arterial disease.
When autologous arteries and veins are unavailable or unsuitable, synthetic polytatrafluoroethylene (PTFE) or Dacron® grafts are often employed to reconstruct or replace damaged or diseased cardiovascular vessels; particularly, in situations where large diameter (i.e. ≧6 mm) vessels are required.
There are, however, numerous drawbacks and disadvantages associated with synthetic prostheses. A major drawback is the poor median patency exhibited by synthetic prostheses, due to stenosis, thromboembolization, calcium deposition and infection. Indeed, it has been found that patency is >25% @ 3 years using synthetic and cryopreserved prostheses in peripheral and coronary bypass surgeries, compared to >70% for autologous vascular conduits. See Chard, et al., Aorta-Coronary Bypass Grafting with Polytetrafluoroehtylene Conduits: Early and Late Outcome in Eight Patients, j Thorac Cardiovasc Surg, vol. 94, pp. 312-134 (1987).
Decellularized bovine internal jugular xenografts and human allograft vessels from cadavers have also employed to reconstruct or replace damaged or diseased cardiovascular vessels. Such materials and structures are, however, prone to calcification and thrombosis and, thus, have not gained significant clinical acceptance.
Vascular prostheses constructed of various biodegradable materials, such as poly (trimethylene carbonate), have also been developed to reconstruct or replace damaged or diseased cardiovascular vessels. There are, however, several drawbacks and disadvantages associated with such prostheses.
One major disadvantage is that the biodegradable materials and, hence, prostheses formed therefrom, often break down at a faster rate than is desirable for the application. A further disadvantage is that the materials can, and in many instances will, break down into large, rigid fragments that can cause obstructions in the interior of the vessel and cause inflammation.
More recently, prostheses comprising various remodelable materials, such as extracellular matrix (ECM®) sheets, have been developed to reconstruct or replace damaged or diseased cardiovascular vessels. Illustrative are the ECM® prostheses disclosed in Applicant's Co-Pending application Ser. No. 13/573,226.
Although such materials and prostheses formed therewith have garnered overwhelming success and, hence, gained significant clinical acceptance, there are a few drawbacks associated with such grafts. Among the drawbacks are the construction and, hence, configuration of the noted prostheses.
As discussed in detail in Co-Pending application Ser. No. 13/573,226, such prostheses typically comprise one or more sheets of ECM tissue, e.g., small intestine submucosa, which is secured at one edge to form a tubular structure. The secured edge or seam can, and in many instances will, disrupt blood flow through the graft. A poorly secured edge also poses a significant risk of thrombosis and cause turbulent flow.
Further, in some instances, wherein the ECM prostheses comprise two or more sheets, i.e. a multi-sheet laminate, the laminate structure may delaminate.
Thus, readily available, versatile tissue prostheses that are not prone to calcification, thrombosis and intimal hyperplasia would fill a substantial and growing clinical need.
It is therefore an object of the present invention to provide tissue prostheses in the form of seamless tubular members (or structures) or graft structures that substantially reduce or eliminate (i) the risk of thrombosis, (ii) intimal hyperplasia after intervention in a vessel, (iii) the harsh biological responses associated with conventional polymeric and metal prostheses, and (iv) the formation of biofilm, inflammation and infection.
It is another object of the present invention to provide tissue prostheses that can effectively replace or improve biological functions or promote the growth of new tissue in a subject.
It is another object of the present invention to provide tissue prostheses that induce “modulated healing” of damaged biological structures and/or damaged tissue associated therewith, including modulation of inflammation, and host tissue proliferation, bioremodeling and regeneration of new tissue and tissue structures with site-specific structural and functional properties.
It is another object of the present invention to provide tissue prostheses that are capable of administering a biologically active and/or pharmacological agent to host tissue and, thereby, produce a desired biological and/or therapeutic effect.